We have established the colonies of LSL-Kras G12D (conditional K-ras mutant), LSL p53 R172 H (conditional p53 mutant), Pdx-1-Cre (pancreas-specific Cre-recombinase transgenic), NOS2- and IL-6 -deficient mice. We have also generated NOS2-deficient LSL-Kras G12D mice. To activate the conditional mutant K-ras and p53 alleles these mice are being bred with Pdx-1-Cre mice. IL-6 deficient mice are crossed with LSL-Kras G12D (conditional K-ras mutant) to generate IL-6-deficient conditional K-ras mutant mice. Following activation, the Kras and p53 double mutant mice will develop PDAC in 3-6 months in more than 90% of mice. These mice will be compared with those Kras and p53 double mutant mice that lack either NOS2 or IL-6 or are treated with anti-MIF antibody.